What is the independent effect of human papillomavirus (HPV) on oropharyngeal cancer survival?
Background: HPV has been associated with oropharyngeal cancer risk and appears to underlie the rising incidence of this disease in the U.S. and Europe. HPV-positive oropharyngeal cancers may be associated with a better prognosis than HPV-negative oropharyngeal cancers.
Study design: Retrospective analysis of HPV tumor status and survival of oropharyngeal cancer patients within a phase III randomized trial for stage III/IV squamous cell carcinoma of the head and neck, including 360 patients receiving accelerated fractionation (concomitant boost) radiotherapy with concurrent cisplatin (experimental arm) and 361 patients receiving standard fractionation radiotherapy with concurrent cisplatin (control arm)
Setting: Within the multi-institutional cooperative Radiation Therapy Oncology Group (RTOG) randomized phase III clinical trial (RTOG 0129)
Synopsis: This study presents the retrospective analysis of HPV tumor status and survival of 323 oropharyngeal cancer patients within RTOG 0129. There was no difference in survival associated with treatment arm. However, there was a significantly lower risk (after multivariate adjustment) for death (58 percent lower) or relapse (51 percent lower) for patients with HPV-positive oropharyngeal cancer as compared with patients with HPV-negative oropharyngeal cancer, and a similar protective effect was seen for tumors overexpressing p16 (another marker of HPV). Smoking status (smoker vs. nonsmoker with cutoff set at <10 pack-years) was the second most important prognostic factor after HPV. N-stage was the third critical prognosticator for patients with HPV-positive cancers, while T-stage was the third critical prognosticator for HPV-negative cancers.
This study is limited by the retrospective analysis of HPV status (unavailable for 25 percent of patients) within a prospective trial with two different treatment arms, potential misclassifications of HPV or smoking status, and possible inability to generalize the findings to patients not treated with radiotherapy. The HPV-tested and unavailable groups, however, were similar with respect to baseline characteristics and survival, major misclassifications are unlikely given the expected demographic and stage characteristics of the HPV-positive group, and virtually all stage III/IV surgically treated oropharyngeal patients will also receive radiation. The sophisticated three-way categorization of risk for death from oropharyngeal cancer may lead to the incorporation of HPV status and possibly smoking status into the staging system and will likely result in treatment modifications.
Bottom line: HPV status is a strong independent prognostic factor for survival among patients with oropharyngeal cancer, and the effect of HPV status on survival appears further modified by smoking history.
Reference: Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. New Engl J Med. 2010;363(1):24-35.
—Reviewed by Erich M. Sturgis, MD, MPH